2008 Stroke July 2017 mRS that depend, in part, on meeting or not meeting the proportional odds assumption. 16, 18 After scientific discussion and debate in the field, investigators designed FDA-approved trials that use the ordinal distribution of the mRS as the primary outcome measure. 20, 21 Although the relative efficiency has not been shown for all possible tests, using the entire distribution of the mRS may have greater statistical power than a dichotomized analyses when the treatment benefit occurs similarly at several levels of the mRS, rather than clustering at just one end, 22 although simulations should be conducted to confirm this for any given hypothesized treatment effect. One disadvantage of the ordinal approach is communicating what a change across the distribution on an ordinal scale means to patients and physicians. Furthermore, the severity distribution of enrolled subjects may affect the ability of the ordinal approach to capture transitions across health states. More recently, the focus has been on patient-centered outcomes or quality of life, and the most widely accepted patientcentered outcome measure is utility—the desirability of a specific health outcome to the patient. 23 A utility of 1 represents excellent health. The STAIR (Stroke Therapy Academic Industry Roundtable) recommended the development of a utility-weighted (UW) version of the mRS. 24 Investigators subsequently calculated utility values for the various levels of the mRS by mapping responses from the EQ-5D (European Quality of Life Scale) 25 onto the mRS levels in populations of patients with stroke. 22, 26, 27 In another study, disability weights for mRS levels were derived using the methodology of the WHOGBD (World Health Organization Global Burden of Disease Project). 28 On the basis of these approaches, a UW-mRS was accomplished (Table 2) and compared with ordinal and dichotomous approaches in 8 previous acute stroke trials. 22, 27, 28 This analysis demonstrated the potential advantages of both the

UW-mRS and the ordinal mRS when compared with the dichotomous analyses. Analysis of the UW-mRS is computationally straightforward, using t tests that compare the mean utility difference between treatment arms, and the UW-mRS can easily be extended to incorporate adjustments of baseline covariates. An additional feature of a utility measure such as the UW-mRS is the ability to generate quality-adjusted-life-years (QALYs) gained or lost by an intervention or treatment. 29–33 A QALY measure assumes that a year of life lived in perfect health is worth 1 QALY (1 year of life× 1 utility value= 1 QALY) and that a year of life lived in a state of less than this perfect health is worth less than one. To determine the exact QALY value, one multiplies the utility value associated with a given state of health by the years lived in that state. For example, 1 year lived with perfect health or 2 years lived at half of the value of perfect health as judged by patients are both equivalent to 1 QALY. To illustrate how QALYs are calculated, let us use a simplified hypothetical example of an acute stroke trial of 1000 subjects in excellent health before the stroke (mRS of 0 and UW-mRS utility of 1) and the mRS distributions observed in the NINDS tPA trials. The effect size at 90 days for intravenous tPA versus placebo in the NINDS tPA trials as measured by the UW-mRS is 0.09 (UW-mRS methodology from the DAWN [DWI or CTP Assessment with Clinical Mismatch in the Triage of Wake-Up and Late Presenting Strokes Undergoing Neurointervention] trial22 as shown in Table 2). The QALY calculation is 0.09 utility difference× 0.25 years= 0.0225 QALYS (or 8.2 quality-of-life days per …